TY  - JOUR
A1  - Subramanian, Hariharan
A1  - Döring, Frank
A1  - Kollert, Sina
A1  - Rukoyatkina, Natalia
A1  - Sturm, Julia
A1  - Gambaryan, Stepan
A1  - Stellzig-Eisenhauer, Angelika
A1  - Meyer-Marcotty, Philipp
A1  - Eigenthaler, Martin
A1  - Wischmeyer, Erhard
T1  - PTH1R Mutants Found in Patients with Primary Failure of Tooth Eruption Disrupt G-Protein Signaling
JF  - PLoS One
N2  - Aim

Primary failure of tooth eruption (PFE) is causally linked to heterozygous mutations of the parathyroid hormone receptor (PTH1R) gene. The mutants described so far lead to exchange of amino acids or truncation of the protein that may result in structural changes of the expressed PTH1R. However, functional effects of these mutations have not been investigated yet.

Materials and Methods

In HEK293 cells, PTH1R wild type was co-transfected with selected PTH1R mutants identified in patients with PFE. The effects on activation of PTH-regulated intracellular signaling pathways were analyzed by ELISA and Western immunoblotting. Differential effects of wild type and mutated PTH1R on TRESK ion channel regulation were analyzed by electrophysiological recordings in Xenopus laevis oocytes.

Results

In HEK293 cells, activation of PTH1R wild type increases cAMP and in response activates cAMP-stimulated protein kinase as detected by phosphorylation of the vasodilator stimulated phosphoprotein (VASP). In contrast, the PTH1R mutants are functionally inactive and mutant PTH1R/Gly452Glu has a dominant negative effect on the signaling of PTH1R wild type. Confocal imaging revealed that wild type PTH1R is expressed on the cell surface, whereas PTH1R/Gly452Glu mutant is mostly retained inside the cell. Furthermore, in contrast to wild type PTH1R which substantially augmented K+ currents of TRESK channels, coupling of mutated PTH1R to TRESK channels was completely abolished.

Conclusions

PTH1R mutations affect intracellular PTH-regulated signaling in vitro. In patients with primary failure of tooth eruption defective signaling of PTH1R mutations is suggested to occur in dento-alveolar cells and thus may lead to impaired tooth movement.
KW  - phosphorylation
KW  - xenopus oocytes
KW  - calcium signaling
KW  - intracellular receptors
KW  - mutation
KW  - teeth
KW  - tooth eruption
KW  - transfection
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147967
VL  - 11
IS  - 11
ER  - 
TY  - JOUR
A1  - Beyrich, Claudia
A1  - Löffler, Jürgen
A1  - Kobsar, Anna
A1  - Speer, Christian P.
A1  - Kneitz, Susanne
A1  - Eigenthaler, Martin
T1  - Infection of Human Coronary Artery Endothelial Cells by Group B Streptococcus Contributes to Dysregulation of Apoptosis, Hemostasis, and Innate Immune Responses [Research Article]
N2  - Early onset sepsis due to group B streptococcus leads to neonatal morbidity, increased mortality, and long-term neurological deficencies. Interaction between septicemic GBS and confluent monolayers of human coronary artery endothelial cells (HCAECs) was analyzed by genome wide expression profiling. In total, 124 genes were differentially expressed (89 upregulated, 35 downregulated) based on a more than 3-fold difference to control HCAEC. Regulated genes are involved in apoptosis, hemostasis, oxidative stress response, infection, and inflammation. Regulation of selected genes and proteins identified in the gene array analysis was confirmed by Real-time RT-PCR assay (granulocy te chemotactic protein 2), ELISA (urokinase, cyclooxygenase 2, granulocyte chemotactic protein 1), and western blotting (Heme oxygenase1, BCL2 interacting protein) at various time points between 4 and 24 hours. These results indicate that GBS infection might influence signalling pathways leading to impaired function of the innate immune system and hemorrhagic and inflammatory complications during GBS sepsis.
KW  - Medizin
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68834
ER  - 
TY  - JOUR
A1  - Loeffler, Claudia
A1  - Loeffler, Jürgen
A1  - Kobsar, Anna
A1  - Speer, Christian P.
A1  - Eigenthaler, Martin
T1  - Septic Vs Colonizing Group B Streptococci Differentially Regulate Inflammation and Apoptosis in Human Coronary Artery Endothelial Cells - a Pilot Study
JF  - Journal of Pediatrics and Neonatal Care
N2  - In this pilot study, we exemplify differences between a septic and a colonizing GBS strain during their interaction with Endothelial Cells by evaluating cytokine levels, surface and apoptosis-related molecules. These preliminary results indicate that in vitro infection using an exemplary septic GBS strain results in diminished activation of the innate immune response.
KW  - streptococci
KW  - apoptosis
KW  - inflammation
KW  - endothelial cells
KW  - innate immunity
KW  - early onset sepsis
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125596
VL  - 2
IS  - 2
ER  -